Amino acidsAmino acids

Lecture 1Dr. Mamoun AhramSummer, 2014

ResourcesResources

This lectureCampbell and Farrell’s Biochemistry, Chapters 3 (pp.66-76)

General structureGeneral structure

(Chiral carbon)

The opposite is achiral

Isomers, stereoisomers, enantiomersIsomers, stereoisomers, enantiomers

• If two molecules have the same number of atoms, they are isomers.

• If the isomers have the same atomic connectivity, but differ spatially, they are stereoisomers.

• If the stereoisomers are mirror images of each other, they are enantiomers.

Light polarizationLight polarization

Optically active compounds can rotate polarized light to the left or the right.

The amino acids that occur in proteins naturally are all of the L form.

Designation of carbonsDesignation of carbons

Side-chain carbon atoms are designated with letters of the Greek alphabet, counting from the -carbon. These carbon atoms are, in turn, the -, -, -, and -carbons. The terminal carbon atom is referred to as the -carbon

Types of amino acidsTypes of amino acids

There are twenty kinds of amino acids depending on the side chains varying in

SizeShapeChargeHydrogen-bonding capacityHydrophobic characterChemical reactivity

Classification (according to R group)Classification (according to R group)

Non-polarPolarCharged(positive)

Charged (negative)

AlanineSerineLysineGlutamate

ValineThreoeineArginineAspartate

LeucineGlutamineHistidine

IsoleucineAsparagine

MehionineCysteine

TryptophanTyrosine

Phenylalanine

Proline

Glycine

GlycineGlycine

Is it chiral?

AlanineAlanine

Valine, leucine, and isoleucineValine, leucine, and isoleucine

These are essential amino acids in the sense that the body cannot synthesize them.

MethionineMethionine

Proline (imino acid)Proline (imino acid)

Secondary nitrogen

GlycineGlycine

Is it chiral?

Serine and threonineSerine and threonine

Cysteine (Cys, C)Cysteine (Cys, C)

Asparagine and glutamineAsparagine and glutamine

Amide groups

MSG in foodMSG in food

Monosodium glutamate, or MSG, is a derivative of glutamic acid used as a flavor enhancer.MSG may cause Chinese

restaurant syndrome (chills, headaches, and dizziness).

Phenylalanine, tyrosine, Tryptophan Phenylalanine, tyrosine, Tryptophan

Lysine and arginineLysine and arginine

guanidinogroup

HistidineHistidine

Aspartic acid and glutamic acidAspartic acid and glutamic acid

QuestionsQuestions

1. Two amino acids are negatively-charged:

2. The following amino acid is achiral:

3. …etc.

Biological significance Biological significance of amino acidsof amino acids

a-nitrogen atom of amino acids is a primary source for many nitrogenous compounds:

HormonesNeurotransmittersBiologically active peptides

Tyrosine (1)Tyrosine (1)

is converted into catecholamine neurotransmittersdopamine NorepinephrineEpinephrine

flight or fight

Tyrosine (2)Tyrosine (2)Tyrosine is converted into

melanin (skin color)Thyroxine (hormone)

Tyrosine and lifeTyrosine and life

Cheese contain high amounts of tyramine, which mimics epinephrine; for many people a cheese omelet in the morning is a favorite way to start the day.

TryptophanTryptophan

Tryptohpan serves as the precursor for the synthesis of Neurotransmitters

serotonin (neurotransmitter-sedative) melatonin (day-night cycle)

HistamineHistamine

• Regulates physiological function in the gut

• Acts as a neurotransmitter• Causes allergic symptoms (a

major causes for asthma) • Contributes to inflammatory

response• Causes constriction of smooth

muscle

GlutamateGlutamate

Is a precursor of - aminobutyric acid (GABA)

Inhibitory neurotransmitter (CNS)

γ- γ- carboxyglutamate (Gla)carboxyglutamate (Gla)

The glutamate residues of some clotting factors are carboxylated to form γ- carboxyglutamate (Gla) residues

Vitamin K is essential for the processThis carboxylation is essential for the function of the clotting factors

ArginineArginine• L-arginine is the precursor of nitric oxide (NO) • NO functions:

• Vasodilation, inhibition of vasoconstriction, inhibition of platelet adhesion, inhibition of leukocyte adhesion, antiproliferative action, scavenging superoxide anion (anti-inflammatory)

Lysine and prolineLysine and proline

Both are hydroxylated and are part of collagen structure.

Why do amino acids get ionized?Why do amino acids get ionized?

Zwitterion and isoelectric point Zwitterion and isoelectric point

At physiological pH, amino acids (without ionizable groups) are electrically neutralZwitterion: a molecule with two opposite charges and a net charge of zero

Effect of pHEffect of pH

Example 1 (alanine)Example 1 (alanine)

Henderson-Hasselbalch Henderson-Hasselbalch EquationEquation

We have calculated the ratio of acid to conjugate base for an -carboxyl group and an -amino group at pH 7.0We can do this for any weak acid and its conjugate base at any pH using the Henderson-Hasselbalch equation

[weak acid]

[conjugate base]log=pH pKa +

Isoelectric PointIsoelectric Point

The pH where the net charge of a molecules such as an amino acid or protein is zero is known as isoelectric point or pIFor the nonpolar and polar amino acids with two pKa’s, the isoelectric point is calculated by taking the numerical average of the carboxyl group pKa and the a-amino group pKa

Ionization of side chainsIonization of side chains

Nine of the 20 amino acids have ionizable side chainsThese amino acids are tyrosine, cysteine, arginine, lysine, histidine, serine, threonine, and aspartic and glutamic acidsEach side chain has its own pKa values for ionization of the side chains

pI of amino acidspI of amino acids

Amino AcidSide Chain

pKa3pI

Arginine12.510.8

Aspartic Acid4.03.0

Cysteine8.05.0Glutamic Acid4.13.2Histidine6.07.5Lysine11.010

Let’s consider pKa of -NH2 = 9 and pKa of –COOH = 2 for all amino acids

Calculation of pICalculation of pI

The isoelectric point for these amino acids is calculated by taking the average of the pKa’s of the groups with same charge when ionizedIn this case, the total charge on the groups with like charge must equal one (1) so that it can be balanced by the one (1) opposite charge present on the molecule

Example: GlutamateExample: Glutamate

To calculate the isoelectric point of Glu, the pKa’s of the two carboxyl groups are averaged.

HistidineHistidine

pI = ~6 (The imidazole group can be uncharged or positively charged near neutral pH).

QuestionsQuestions

1. Draw the titration curve of histidine.

2. What is the ratio of conjugate base/acid of glutamate at pH 4.5?

3. What is the total charge of lysine at pH 7?

What do you need to know?What do you need to know?

The names of amino acidsThe special structural features of amino acidsTheir abbreviations or designationsThe uncommon amino acids, their precursor and function (if any)The pKa of groups

not exact numbers, but which ones are acidic, basic, or near neutral